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Biomedical subjects

S Cohen

Publications and source records attributed to S Cohen.

At least 1,081 records · Page 60Linked to original sources
PubMed1977

Suppression of B cell MIF production by T cells and soluble T cell-derived factors.

Purified populations of guinea pig B cells from nonimmunized animals may be stimualted by PPD or LPS to produce MIF. Unfractionated lymphocyte suspensions from these animals do not produce MIF under these conditions. Reconstitution of B cells with T cells abolishes their ability to generate detectable MIF. A soluble factor obtained from stimulated T cell cultures (MIFIF) is also capable of suppressing this B cell activity. Thus suppressor T cells can interfere with lymphokine production by B cells and this effect is mediated at least in part by a soluble factor. This previously undescribed capacity of T cells may provide an explanation for the fact that B cells do not appear to play a role in reactions of cell-mediated immunity in vivo.

Animals↗
PubMed1977

The role of cell-mediated immunity in the induction of inflammatory responses. Parke-Davis Award Lecture, 1977.

Reactions of cell-mediated immunity fall into two broad categories: those that involve direct participation of intact lymphocytes in the effector mechanism of the reaction and those that involve mediation by soluble lymphocyte-derived factors known as lymphokines. The first kind of reaction is essentially limited to lymphocyte-dependent cytotoxicity, although certain aspects of T cell-B cell cooperation may fall into this category as well. The second category appears to comprise the bulk of the so-called cell-mediated immune response and provides a link between this system and the inflammatory system. Various lymphokines have been shown to exert profound influence upon inflammatory cell metabolism, cell surface properties, patterns of cell migration, and the activation of cells for various biologic activities involved in host defense. Although substantial information is now available about various physicochemical as well as biologic properties of lymphokines, purification and characterization data are as yet too incomplete to allow us to ascribe all of these activities to discrete mediator molecules. Current work involving the development of antibody-based techniques for mediator assay may shed light on this issue. Information on the kinds of cells capable of lymphokine production is now available. Contrary to prior expectation, T cells are not unique in their capacity for lymphokine production. Under appropriate circumstances, B cells and even nonlymphoid cells can do so as well. The unique property of lymphocytes in this regard appears to relate to their ability to respond to certain specialized signals such as specific antigen or an appropriate mitogen. Mediator production per se may represent a general biologic phenomenon. Although lymphokines have been defined mainly in terms of in vitro assays, early speculations about their in vivo importance are proving correct. Evidence for the role of lymphokines comes from studies involving detection of lymphokines in tissues, studies involving injection of exogenous lymphokines, and studies involving suppression of in vivo reactions by various techniques. The use of antilymphokine antibodies has proven useful in the latter kinds of experiments. Work in many laboratories is beginning to relate these findings to clinically relevant situations. A major unsolved problem relates to the regulation and control of lymphokine production and activity. At present only a limited body of information is available on this point. This is a potentially fruitful area for future investigation since it may provide techniques for manipulating the immune system in ways that are clinically useful.

Animals↗
PubMed1977

Subpopulations of lymphocytes to produce various lymphokines. I. Function of subpopulations separated by velocity sedimentation.

Identification of a subpopulation of lymphocytes producing lymphokines was attempted by fractionating the lymph node cells from guinea pigs immune to DNP-BSA by velocity sedimentation at 1 x G. Each of six fractions obtained by this procedure was cultured with or without the presence of antigen, and the culture supernatants that were separated 24 hr later were assayed for various lymphokine activities. Most of the lymphokines, including migration inhibition factor, chemotactic factor for neutrophils, mitogenic factor, and lymphotoxin were generated by the first two fractions of lymphocytes, which represented the largest, most rapidly sedimenting cells. Although th procedure of cell separation does not depend on cell surface properties, the larger cells contained more cells with T cell surface markers and the smalller contained more cells with B cell surface markers. Proliferative response of those lymphocytes measured by 3H-thymidine uptake, however, has shown that the largest two subpopulations responded poorly either to specific antigens or to mitogens (PHA and LPS), and rather that the medium size cells responded most strongly to the both stimulants. These results indicated that the production of some lymphokines confined to certain subpopulations of lymphocytes which are large in size. Further, these cells are readily separable from the medium sized cells that respond strongly to antigenic and mitogenic stimuli with mitogenic responses.

Animals↗
PubMed1977

Inhibition of the lethality of bleomycin A5 in L-cells by hirudonine.

The lethality of several individual bleomycin derivatives, i.e., the spermidine derivative (A5), The dimethyl sulfonium aminopropyl derivative (A2), and the agmatine derivative (B2), was compared on mouse fibroblasts. The spermidine derivative, bleomycin A5, was the most toxic, producing more than a 2-log drop in clonability in 50 hr at 20 microng/ml. 6-Azauridine, a relatively nonlethal inhibitor of RNA synthesis and cell multiplication, produced a 60% decrease of adenine incorporation into nucleic acids without inhibiting the lethal action of A5. This result differed from the effects of inhibition of RNA synthesis on the lethality of A5 in Escherichia coli. Hirudonine (1,8-diamidino-spermidine) markedly and specifically inhibited the lethal effects of A5 in L-cells but not in E. coli. However, hirudonine did not affect the toxicity of A2 and B2, separately or together, as it did in the mixture used clinically. Nor did arcaine (diamindinoputrescine) reduce the lethality of the agmatine (monoamidinoputrescine) derivative, B2.

Amidines↗
PubMed1977

Evidence that abnormal myoelectrical activity produces colonic motor dysfunction in the irritable bowel syndrome.

Although the irritable bowel syndrome is characterized as an abnormality in colonic motor activity occurring in response to certain stimuli, the etiology of this disorder is unclear. The purpose of this study is to determine the relationship of altered slow wave activity and the abnormal motility of the distal colon seen in patients with the irritable bowel syndrome. Myoelectrical activity was recorded using a bipolar electrode clipped to the distal colonic mucosa and motor activity was measured by perfused catheters. Colonic slow waves and contractions were present at two frequencies, 6 and 3 cycles per min. The slow wave frequency seemed to determine the frequency of colonic motor activity. Patients with the irritable bowel syndrome had increased 3-cycle per min slow wave activity in the basal state (P less than 0.001). However, no difference in basal 3-cycle per min motor activity was present between the two groups (P greater than 0.05). When colonic motor activity was increased with cholecystokinin or pentagastrin, patients with irritable bowel syndrome showed a marked increase in 3-cycle per min contractile activity, occurring simultaneously with 3-cycle per min slow wave activity. These studies suggest that increased colonic 3-cycle per min slow wave activity in patients with the irritable bowel syndrome may be the basic abnormality that leads to colonic motor dysfunction in response to various physiological stimuli.

Adult↗
PubMed1977

Effect of vasoactive intestinal polypeptide on basal and cholecystokinin-induced gallbladder pressure.

Studies were conducted in vivo to examine the pressure response of the opossum gallbladder to vasoactive intestinal polypeptide (VIP) alone and in combination with cholecystokinin (CCK). The following observations were made (1) VIP alone produced dose-related decreases in basal gallbladder pressure; (2) VIP eliminated spontaneous contractile activity when present; (3) VIP significantly antagonized the expected pressure response to CCK infusion. These observations lend further support to our proposal that the regulation of gallbladder motor function depends upon the actions and interactions of the gastrointestinal hormones on gallbladder smooth muscle.

Animals↗
PubMed1976

Transformation by murine and feline sarcoma viruses specifically blocks binding of epidermal growth factor to cells.

Normal cells in culture have membrane receptors for epidermal growth factor (EGF); EGF stimulates cells to divide by binding to these receptors. Cells transformed by murine and feline sarcoma viruses rapidly lose the ability to bind EGF, whereas cells transformed by the DNA tumour viruses, polyoma and SV40, or infected with non-transforming RNA tumour viruses have normal levels of functional EGF receptors. The results suggest that a product of the sarcoma virus genome specifically changes cell EGF receptors; the sarcoma gene product may, then, be functionally related to EGF.

Binding Sites↗
PubMed1976

Conformation and unfolding thermodynamics of epidermal growth factor and derivatives.

Mouse submaxillary epidermal growth factor (EGF) is a 53-residue single chain peptide hormone of known amino acid sequence which contains three disulfides, five tyrosines, and two tryptophans. Circular dichroic (CD) spectra have been obtained and resolved for EGF, several well-characterized chemical and enzymic derivatives, and related low molecular weight model compounds. Assignments have been made to most of the resolved bands; these include the peptide, aromatic, and disulfide chromophores. From a comparison of the rotational strength of the 213-nm resolved CD band in native EGF with that of standard proteins, EGF is estimated to contain about 22% beta structure and no alpha helicity. A derivative of EGF lacking the five carboxyl-terminal residues (prepared by limited trypsin digestion) and the cyanogen bromide derivative, in which there is a single main-chain cleavage at residue 21, have spectra properties indicative of approximately 10 and 12% beta structure, respectively. The near-ultraviolet CD spectra of the derivatives are similar to, albeit not identical with, that of EGF. The rotational strengths characteristic of the side-chain chromophores in EGF and these derivatives are several-fold higher than the corresponding values in low molecular weight model compounds. Thus, it appears that EGF and these modified forms contain a stable (and similar) tertiary structure. In contrast, the S-aminoethylated derivative of EGF exhibits a drastically altered CD spectrum relative to EGF indicating a different conformation(s). Equilibrium studies on the guanidinium hydrochloride (GdmCl) mediated reversible unfolding of EGF showed that the transition midpoint is quite high (i.e., 6.89 M GdmCl at 25.0 degrees C), thus, indicating considerable stability. From these data a rough estimate of 16 kcal/mol can be made for the unfolding free energy (delta G degrees) of EGF in the absence of denaturant. Interestingly, EGF exhibits greater stability characteristics than several proteins two to four times its size. The cyanogen bromide derivative of EGF exhibited greatly reduced stability characteristics, e.g., the transition midpoint occurred at 4.19 M GdmCl (25.0 degrees C) and delta G degrees was estimated to be approximately 4 kcal/mol. Thus, a single main-chain cleavage reduced the stability of EGF by about 70%. Thermal transitions of EGF and the cyanogen bromide derivative in the presence of concentrated GdmCl are characterized by a relatively high enthalpy of about 25 kcal/mol at 40 degrees C and a low (probably zero) heat capacity. From these thermodynamic parameters one can calculate that the large reduction in delta G degrees due to scission of the single peptide bond between residues 21 and 22 can be attributed almost completely to a change in entropy; e.g., at 40 degrees C the apparent entropy of unfolding of EGF is 20.4 cal mol-1 deg-1 while that of the cyanogen bromide derivative is 66.4 cal mol-1 deg-1.

Amino Acid Sequence↗